engleski

Development of functional wound-dressings with chitosan and melatonin therapeutic (nano)systems

Wound healing is a dynamic well-coordinated biological process involving complex interactions among cells, extracellular matrix components and signalling compounds, resulting in wound closure. Healing process is usually divided into four overlapping phases – haemostasis, inflammation, proliferation and remodelling. Many internal and external factors, with infection being the most common one, can disrupt the healing cascade and subsequently lead to chronic and nonhealing states. Accompanied with growing bacterial resistance, design of functional wound dressings that provide adequate conditions for healing in terms moist environment, gas exchange, protection from external contamination and drug delivery, represents a great imperative and challenge. In this thesis, novel chitosan-based wound dressing in the form of dry powder was developed by spray drying technology and evaluated and compared with complementary microparticulate dressings. Three variants of melatonin loaded wound dressings were evaluated - chitosan, chitosan/Pluronic® F127 and NLC enriched chitosan/Pluronic® F127 microspheres. Dressings were designed in form of dry powder that swells in contact with wound exudate, forming an in situ hydrogel. Therefore, dressings were characterized in terms of physico-chemical properties, in vitro drug release, moisture related properties, antibacterial efficacy, in vitro biocompatibility with skin cell lines, in vitro healing potential and long-term stability in dry state. Melatonin loaded NLC enriched chitosan/Pluronic® F127 microspheres was optimized employing definitive screening design. NLC enriched microspheres showed improved flowability features and prolonged drug release when exposed to slightly acidic conditions, as well as lower fluid uptake capacity, water vapour transition and evaporation rate. Melatonin loaded chitosan/Pluronic® F127 microspheres were shown to be suitable for application as dressing for wounds that produce high amounts of exudate, while NLC enriched microspheres were more appropriate for application to moderately exuding wounds. Tested systems showed antimicrobial activity and biofilm inhibition/eradication potential against S. aureus ATCC and S. aureus MRSA strains. Melatonin loaded NLC enriched and NLC free chitosan/Pluronic® F127 microspheres were shown as biocompatible with dermal keratinocytes and fibroblasts in vitro, with respectable potential to promote wound healing process. Powders in dry state demonstrated good long-term stability. Conclusively, proposed in situ forming dressings showed the complementary potential to improve healing of different types of chronic wounds by maintaining favourable moist environment, while providing antibacterial shelter.

melatonin ; chitosan ; microspheres ; spray drying ; NLC ; wound healing

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